The Lp lipoprotein has been associated with coronary heart disease (CHD) in Scandinavian studies. Its level is largely controlled by genetic factors but a major gene effect has been questioned. This project will examine the assocation of LP with CHD in a population-based case-control study among participants of the Honolulu Heart Study and its inheritance in their families. Men sustaining myocardial infarction (MI) in this cohort of Japaneses ancestry have been systematically identified and approximately 250 of them will be available for study. These will be supplemented with 100 cases of angina. 350 age-matched control men free of CHD will be randomly chosen from the population. Lp lipoprotein levels will be estimated by three methods (Ouchterlony, lipoprotein electrophoresis, and rocket immunoelectrophoresis) without knowledge of disease status. Confounding variables including total and HDL cholesterol, triglyceride, obesity, smoking, alcohol use, and blood pressure will be measured. Analysis will focus on the relative risk associated with LP lipoprotein, and whether this risk is independent of the risk factors. The three methods of LP determinations will be compared with respect to reproducibility and ability to discriminate CHD cases and controls. For genetic analysis the families of 200 men believed to have high levels of LP (based on a previously identified "sinking" pre-beta lipoprotein) and of 50 control men will be studied. About 250 wives and 600 children are anticipated. Lp lipoprotein will be estimated by the same three methods without knowledge of subject identity. Esterase D will be tested in a separate laboratory. Segregation analysis using a mixed model allowing for both major gene and polygenic effects will be used to resolve the issue of a major locus. Decisive evidence on possible genetic linkage with esterase D is also expected. This project should settle the question of a major gene controlling Lp and should clarify the role of this obscure but apparently important lipoprotein as a risk factor for CHD.